PB2045: USE OF ANAKINRA IN THE TREATMENT OF ADULT HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS: A SYSTEMATIC REVIEW
Authors: Ali Eshaghpour, Rachel Foote, Rachael Principato, Mark Crowther
Journal: HemaSphere (2023)

Topic: 12. Bone marrow failure syndromes incl. PNH - Clinical Background: Hemophagocytic lymphohistiocytosis (HLH) is a rare syndrome characterized by extreme inflammation and tissue destruction through immune activation of T cells, NK cells, and macrophages leading to a cytokine storm. HLH is traditionally classified as primary and secondary. While primary HLH is typically familial and seen in pediatric populations, secondary HLH is often caused by autoimmune diseases, infectious diseases, and malignancies. While underlying incidence is very low, HLH is associated with significant mortality reaching near 100% when untreated, and 50-75% with traditional chemotherapy-based treatment regimens. Recently, treatment regimens have increasingly included Anakinra, an IL-1 Receptor antagonist. The evidence for the use of Anakinra is primarily founded upon pediatric literature, while there is very limited evidence for its use in adult patients. Aims: To synthesize the existing primary evidence for Anakinra use in adult patients with HLH. Methods: A comprehensive search of MEDLINE, Embase, and the grey literature was done from inception to December 2022. Studies were screened at abstract and full-text level independently and in duplicate. All English language retrospective cohort, prospective cohort, and randomized controlled studies investigating the use of Anakinra in adult patients with HLH and related hemophagocytic disorders (I.e., macrophage activation syndrome) were included. Baseline characteristics, underlying diagnoses, HLH lab parameters, details of Anakinra regimen, concurrent therapy, and comparator group therapy were recorded. The primary outcome measure was mortality as defined by the primary study. Secondary outcomes include length of hospitalization, length of ICU stay, clinical remission, relapse rate, and resolution of inflammatory markers. Results: Of the 1591 studies screened, eight studies with a total of 81 unique patients were included in the analysis. Studies included patients with various etiologies of HLH, most commonly autoimmune, malignant, and infectious. The median Anakinra dosage was 530 mg total per day (range: 100mg, 2400 mg) given either subcutaneously, intravenously, or via intravenous infusion. Steroids were included as concurrent therapy in all studies, with some studies including other immunosuppressive therapy including IVIG, cyclosporine, cyclophosphamide, tocilizumab, etoposide, and ruxolitinib. Median mortality rate was 45% (Range: 12.5%, 69%). Total mortality rate of all included patients was 42% (34/81). Summary/Conclusion: Regardless of available treatment HLH is associated with very high mortality. Given the low incidence of HLH and importance of individual patient factors, treatment regimens need to be personalized. Anakinra may have benefit in conjunction with conventional therapy in certain cases. Given its relative ease of administration and low toxicity as compared to chemotherapy-based regimens, use of Anakinra may be preferred. Evidence regarding potential benefit and dosing regimens is extremely limited. Further observational studies are required to reliably demonstrate the efficacy of Anakinra in HLH.Keywords: Immunosuppressive therapy, Hemophagocytic Lymphohistiocytosis (HLH)